Enveloped viruses deliver their genomes to cells by fusing with cellular membranes. This fusion process is mediated by viral envelope glycoproteins when they undergo conformational changes while binding target cells. For many viruses, including HIV, receptor binding triggers conformational changes in the envelope glycoprotein that are required for mediating membrane fusion required for entry. Our research aims to elucide the roles of CD4 and chemokine receptors in triggering conformational changes in the HIV envelope glycoprotein required for entry. We are focusing on how the receptors affect the structure of the helical regions in gp41 that we have shown to undergo conformational changes critical for HIV entry. Using a peptide corresponding to the C-terminal heptad repeat in the gp41 ectodomain (DP178), we have found that envelope glycoproteins from different strains use receptors differently for triggering conformational changes. We are sorting out how receptor usage correlates with conformational changes, envelope glycoprotein stability, and fusion phenotype (syncytia-inducing or non-inducing strains). More recently we have also shown that a different gp41 peptide inhibitor corresponding to the N terminal heptad repeat also binds gp41 in a receptor-dependent manner. We are comparing and contrasting how these peptides bind and interfere with conformational changes required for HIV entry.